The elderly are more susceptible to many infectious diseases, and yet vaccinating this population is less effective when vaccines that are designed for young individuals are used. To design a vaccine or post-exposure therapy that can protect the elderly against infectious disease it is first necessary to understand how the aging immune response differs from younger individuals when it encounters a pathogen. Using the aging mouse model of tuberculosis we have found that old mice express a transient early resistance to infection that correlates with the presence of CD8 T cells within the lungs. This identifies a previously unrecognized novel immune mechanism in old mice that is clearly absent from the lungs of young mice. The CD8 T cell may therefore be a potential target population for the design of vaccines or novel post-exposure therapies for the elderly. Using the low dose aerosol infection model of tuberculosis we will characterize this CD8 T cell population further by determining when CD8 T cells become more active within the lungs of old mice and the mechanism by which CD8 T cells mediate early resistance. Studies will be carried out in a new BSL-3 facility at Colorado State University and will use old wild type, gene-disrupted, or transgenic mice from our existing in-house aging mouse colonies. The technical approaches will use a combination of flow cytometry, immuno-histochemical staining, and real-time PCR, to address the proposed aims.